1. Field of the Invention
The invention relates to a procedure for the production of a formulation for parenterally administrable pharmaceutical preparations having a liposome dispersion as a carrier for the pharmaceutical active compound, an aqueous predispersion of amphiphilic substances beings fed to a high-pressure homogenizer for the preparation of the liposome dispersion.
2. Description of Related Art
A large number of procedures have been described for the preparation of liposomes (see, for example, Arndt, "Liposomes", Akademie-Verlag Berlin, 1986). The subject of these studies are often experiments on the laboratory scale. A customary starting process here is the dissolution of phospholipids in organic solvents which are removed again before the homogenization in the course of the further preparation process (DE 35 15 335).
A process of the type described in the foregoing Field of the Invention is described in principle in DE 42 07 481.
In the direct dispersion procedure according to DE 42 07 481, the phospholipid and the crystalline active compound are dispersed directly in water. After swelling of the phospholipids in water coarsely divided liposomes first result, which must then be mechanically comminuted. The active compound deposits or accumulates here on the resulting lipid bilayers of the resulting liposomes. Since many liposome formulations are not heat-sterilizable (particle aggregation, phospholipid hydrolysis), comminution of the liposomes by high-pressure homogenization is necessary until the liposomal dispersion can be sterile-filtered (particle size &lt;200 nm).
Comminution in this case takes place in two steps:
a) First the liposome dispersion is comminuted using a high-speed rotor/stator machine to particle sizes of 500 to 5000 .mu.m. PA1 b) Then a fine comminution takes place to particle sizes of 40 to 100 nm using high-pressure homogenizers known per se. PA1 Preparation and provision of stable, liposomal formulations, in particular with active compounds which are poorly soluble in water PA1 Achievement of a narrow particle size distribution with high reproducibility PA1 Gentle treatment, in particular of temperature-sensitive active compounds PA1 Problem-free and accurate scale-up due to modular construction of the nozzle homogenizer device PA1 Reduction of contamination sources due to minimization of nozzle abrasion and use of a high-pressure diaphragm-type reciprocating pump PA1 Good purification possibilities as a result of low gap and dead-space construction PA1 Improved service lives of the unit.